The long-term objective of this research program is to understand the structural and functional organization of the cerebral cortex. Our ongoing investigations have addressed this issue by investigating intrinsic connections and cortical architecture in the sensory and limbic regions of the primate cortex. From the results of these studies in the auditory cortices of the superior temporal region we have drived several organizational principles of cortical connectivity. Chief among these is the principle that a progressive architectonic elaboration of cortical areas is accompanied by an orderly pattern of local cortical connections including their specific laminar origin and termination. Our proposed investigations will test the applicability of these principles in other cortical regions as well as to subcortical connectivity. These investigations will be focused in the cortex of the superior temporal region, the posterior parahippocampal gyrus, and the posterior cingulate cortex and will utilize light microscopic axonal tracing techniques, including radioactively labeled amino acids, fluorescent retrograde tracers and horseradish peroxidase. The data will be analyzed to elucidate both intrinsic cortical connectivity as well as specific thalamocortical connections and connections of the posterior cingulate and parahippocampal cortices with the caudally adjacent visual cortex. We will also investigate the ultrastructural characteristics of afferent termination in the auditory cortex, utilizing the Golgi-EM and HRP-EM procedures in combination with lesion-induced degeneration to characterize afferent termination on identified local circuit and projection neurons. In the cingulate cortex we will localize both opiate and muscarinic acetylcholine receptor complexes utilizing in vitro receptor binding techniques combined with lesions in the thalamus to investigate the association of these receptors with thalamocortical afferents. Finally, in the posterior parahippocampal gyrus, on the basis of some of the known cortical connections of this area, we will utilize the ablation behavior method to investigate the role of this area in visuospatial learning and memory. The application of these different methods of analysis to the primate cerebral cortex are aimed at acquiring sufficient insight into the connections, function, synaptic and transmitter specific receptor characteristics that may ultimately aid in the understanding and treatment of neurological disease.